doi: 10

doi: 10.1128/JVI.00326-10. gut microbiome in regulating host vaccine immunity. However, it remains unclear whether gut microbiome-derived metabolites can improve the immune efficacy of rabies vaccines. As one of the most extensively studied metabolites originating from the gut microbiome, short-chain fatty acids (SCFAs), such as acetate (C2), propionate (C3), and butyrate (C4) (14), reach concentrations exceeding 0.1?mol/kg in the human colon (15) and have multiple beneficial effects on the immune response of the host (16), including powerful anti-inflammatory (17), anti-allergic (18), anti-tumor effects (19), as well as the maintenance of energy metabolism homeostasis (20). The mechanism by which SCFAs exert their biological functions is usually through inhibiting histone deacetylases (HDACs) and activating downstream signaling pathways as ligands for G protein-coupled receptors (GPRs, e.g., GPR41, GPR43, GPR109A, and Olfr78) (16). Notably, the conclusion regarding the impact of SCFAs on humoral immunity is usually conflicting, as some researchers suggest that SCFAs promote optimal antibody responses and immune reactions following Citrobacter contamination by enhancing B cell metabolism, plasma cell differentiation, and antibody production (20). However, Sanchez et al. indicated that a low dose of SCFAs slightly assists the host immune response, while excessive SCFAs inhibit rather than promote the host immune response to ovalbumin (OVA) and autoimmunity in mouse lupus models by upregulating miRNAs targeting Acida and Prdm1 mRNA-3 UTRs through HDAC inhibition (21). Therefore, it is advantageous to investigate whether SCFAs contribute to the Homocarbonyltopsentin immunogenicity of vaccines, especially oral and parenteral vaccines, further confirming their immunomodulatory role. Considering the impairment effect of Vanco around the humoral immune response to rabies vaccines and the important role of SCFAs in host immune response, the aim of this study was Homocarbonyltopsentin to investigate the beneficial effect of SCFA supplementation around the humoral immune response to rabies vaccine in Vanco-treated mice. Our results showed that Vanco significantly altered the SCFAs levels in cecal contents, serum, and inguinal lymph nodes based on targeted metabolomics, with butyrate exhibiting the highest fold change. Oral gavage of Vanco-treated mice with butyrate-producing bacteria (is usually acetate Keratin 7 antibody (corresponding to acetic acid) (22,C25), and the major metabolite of is usually butyrate (corresponding to butyric acid) (26). Therefore, we first verified the abundance of representative SCFA-producing bacteria through qPCR to ensure the depletion of SCFA-producing bacteria by Vanco treatment. Compared with the untreated group, the abundance of (Fig. 1A) and (Fig. 1B) in the Vanco group was significantly reduced. Additionally, we found that the cecum tissue of the Vanco group was larger (Fig. 1C) and the contents (Fig. 1D) were more than that of the untreated group. Open in a separate window FIG 1 Vanco treatment alters the abundance of SCFA-producing bacteria and SCFA levels. Mice were orally administered with 0.5g/L vancomycin for 4?weeks, while the untreated group served as control (Untreated, test. Vanco treatment has been shown to decrease the SCFAs content in cecal contents, thus increasing IL-17-producing T cells (23) and altering the SCFAs content in stools, cecum, tumors, and tumor-draining lymph nodes (TDLNs), thereby changing the anti-tumor effect of radiation therapy (RT) (27). Based on these findings, we aimed to investigate whether Vanco treatment could also alter the SCFAs content in key indicators of serum and inguinal lymph nodes during mouse rabies vaccine immunization using gas chromatography-mass spectrometry (GC-MS). The results showed that SCFAs could be detected in the cecal contents (Fig. 1E), serum (Fig. 1F), and inguinal lymph nodes (Fig. 1G), with higher levels in the cecal contents than in other tissues. Acetic acid had a higher level than propionic acid and butyric acid, but the fold change of butyric acid (untreated/Vanco) was higher than Homocarbonyltopsentin that of acetic acid and Homocarbonyltopsentin propionic acid (Fig. 1H to ?toJ).J). Specifically, the average fold change of butyric acid in the cecal contents was 82.11 (Fig. 1H), in the serum was 1.25 (Fig. 1I), and in the inguinal lymph nodes Homocarbonyltopsentin was 1.40 (Fig. 1J). In summary, Vanco treatment significantly reduces the abundance of SCFA-producing bacteria and the content of SCFAs, with butyric acid exhibiting the highest fold change. Butyrate-producing bacteria and butyrate supplementation enhance the RABV-specific antibody production in Vanco-treated mice. Given.

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